The Effect of Outpatient Ketamine Infusion on Chronic Neuropathic Pain and PTSD

Official title

The Effect of Outpatient Ketamine Infusion on Chronic Neuropathic Pain and PTSD: A Prospective Randomized Design

Overview

This study is aimed to evaluate outpatient ketamine infusion within a military chronic neuropathic pain population and its effect on PTSD. Currently, this is a pilot study with 30 participants. Participants will be randomized to (1) a moderate dose ketamine, (2) moderate dose ketamine +Mg, or (3) a magnesium control group. Participants will complete self-reported pain and PTSD questionnaires throughout the \~24-week study period. The outlined strategy will provide evidence for the utility of ketamine in neuropathic pain management and pain associated comorbidities within a military population.

Detailed description

Subjects will be recruited with no target toward ethnicity, gender, or race. Active duty, veteran, retiree, and military dependents between the ages of 18-70 years old with an established diagnosis of chronic neuropathic pain will be identified and screened for study inclusion. Enrollees will have had neuropathic pain \>3 months duration, report a pain score between 4-7, and meet inclusion/exclusion criteria for the study. Since ketamine's influence on PTSD is a secondary measure, any patients with a PCL-5 score \> 33 will be noted. After informed consent is obtained participants will be randomized into a (1) moderate dose ketamine, (2) moderate dose ketamine +Mg, or (3) a magnesium control group. The magnesium-only group will be randomly assigned to one of the treatment groups (moderate dose ketamine or moderate dose ketamine +Mg) after 2 weeks and complete the full infusion treatment regime of the randomly selected treatment group. Administration of ketamine will occur in diminishing number of dosing events: Week 1 \& 2 will consist of 3 treatments per week. Weeks 3 \& 4 will consist of 2 treatments per week. Weeks 5 \& 6 will consist of 1 treatment per week. Booster treatments will be administered week 10 and week 24. Booster treatments will only be 1 infusion that week. Participants will fill out questionnaires before and after each infusion- day concerning their pain, PTSD, anxiety, depression, and quality of life. Participants will be evaluated at least 5 days prior to the first treatment and 30-35 days after the final infusion. Participants will continue their current pain management regimen during the study and be instructed to use analgesics only as needed. Pain medication use will be recorded throughout the study.

Interventions

• Drug Ketamine
  Ketamine will be placed in 250 mL normal saline and infused at a rate of 62.5 mL/hr. Participants will receive intravenous infusions of ketamine for 4 hours each day in diminishing number of dosing events per week for the full 24-week infusion regime in an outpatient setting. (ketamine 0.5 mg/kg IBW/hr)
• Drug Magnesium sulfate
  Magnesium sulfate 3 grams will be diluted into 250 mL normal saline and infused at a rate of 62.5 mL/hr (over 4 hours until the entire contents are infused and then flushed with 20 mL of normal saline). The Mg only group will be randomly assigned to one of the treatment groups (moderate dose ketamine, or moderate dose ketamine +Mg) after 2 weeks and complete the full 24-week infusion treatment regime of the randomly selected treatment group in an outpatient setting.
• Drug Ketamine + Magnesium sulfate
  Participants will receive intravenous infusions of ketamine and magnesium sulfate in combination. Ketamine will be placed in 250 mL normal saline and infused at a rate of 62.5 mL/hr Participants will receive intravenous infusions of ketamine and magnesium sulfate for 4 hours each day in diminishing number of dosing events per week for the full 24-week infusion regime in an outpatient setting. (Ketamine 0.5 mg/kg IBW/hr + magnesium sulfate 3 grams diluted into 250 mL normal saline)

Primary outcome measures

• Defense and Veterans Pain Rating Score (DVPRS) [Time frame: Up to 32 weeks]
• Brief Pain Inventory Scale (BPI) [Time frame: Up to 32 weeks]
• Life Satisfaction Questionnaire (LiSAT) [Time frame: Up to 32 weeks]
• Post-traumatic Stress Disorder Checklist (PCL-5) [Time frame: Up to 32 weeks]
• The Patient-Reported Outcomes Measurement Information System (PROMIS 29+2) [Time frame: Up to 32 weeks]
• Patient Health Questionnaire-9 (PHQ-9) [Time frame: Up to 32 weeks]
• Generalized Anxiety Disorder Scale [Time frame: Up to 32 weeks]

Secondary outcome measures (3)

• Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS) Tool [Time frame: Up to 32 weeks]
• Richmond Agitation-Sedation Scale (RASS) [Time frame: Up to 26 weeks]
• Clinician-Administered Dissociative States Scale (CADSS) [Time frame: Up to 26 weeks]

Eligibility criteria

Inclusion criteria

• 18-70 years old with Chronic Neuropathic Pain >= 3 months
• Biologic male or biologic female
• Women of childbearing age will be included if there are no plans of pregnancy within the study period, the participant agrees to actively utilize contraception throughout the study, and agrees to pregnancy tests
• Active Duty, Veterans, and retirees
• Ketamine naïve for 1 year
• Moderate Neuropathic pain Scale 4-7

Exclusion criteria

• Cognitive dysfunction
• Psychiatric illness involving psychosis
• Neurocognitive disorder
• Patients with Traumatic Brain Injury (TBI)
• Acute cardiovascular disease or poorly controlled hypertension
• Untreated or uncontrolled thyroid disease
• Hyperthyroidism
• Severe liver or renal disease
• Renal impairment
• History of recent heart attack, vascular disease, or any other medical condition that may be deemed by a provider as a contraindication to receiving ketamine
• Active substance abuse
• Pregnant or lactating
• Patients who are planning to become pregnant within 12 weeks of treatment completion
• Elevated Blood Pressure/hypertension
• Known hypersensitivity to Ketamine
• Hemodynamic instability
• Respiratory depression
• Use of Theophylline or Aminophylline, Sympathomimetics and Vasopressin,
• Use of Benzodiazepines
• A history of drug abuse or dependence
• Active risk of substance use
• Patients who are not able to abide by the pre-treatment and posttreatment clinical protocol, such as food intake, abstaining from certain medications, unable to remain in the clinic for a minimum of 1 hour for observation, and cannot provide the name and phone number of the party who will pick them up post-treatment

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Factorial

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 1 center

• Brooke Army Medical Center — San Antonio

Publications

• Urits I, Jung JW, Amgalan A, Fortier L, Anya A, Wesp B, Orhurhu V, Cornett EM, Kaye AD, Imani F, Varrassi G, Liu H, Viswanath O. Utilization of Magnesium for the Treatment of Chronic Pain. Anesth Pain Med. 2021 Feb 6;11(1):e112348. doi: 10.5812/aapm.112348. eCollection 2021 Feb. PMID 34221945
• Orhurhu V, Orhurhu MS, Bhatia A, Cohen SP. Ketamine Infusions for Chronic Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Anesth Analg. 2019 Jul;129(1):241-254. doi: 10.1213/ANE.0000000000004185. PMID 31082965

Identifiers

NCT: NCT06414356 · 954942

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗